Skin aging and wrinkling is a multifactor process. The formation of lines and wrinkles can be attributed to both extrinsic and intrinsic causes. Extrinsic causes include exposure to ultraviolet radiation and unquenched reactive oxygen species, smoke and other pollutants. Intrinsic factors include degradation of the skin matrix, loss of volume (fat and bone) and muscle tone.
With each smile, squint, laugh, or frown, the contraction of facial muscles causes dynamic wrinkles to appear on the face. In chronologically-younger skin, these lines dissipate quickly and are not prominent. However, with age, the lines become deeper and appear more noticeable. Most commonly, they are manifested as deep furrows between the eyebrows (“frown lines”), at the sides of the eyes (“crow's feet”), and across the forehead (“glabellar lines”).
The biochemistry and biomechanics of skeletal muscle contraction are well-characterized. Contraction is initiated by an electric signal (action potential) transmitted by the motor neuron. At the neuromuscular junction, the action potential causes vesicles to release the neurotransmitter acetylcholine (“Ach”) which, in turn, diffuses across the synapse between the nerve ending and the sarcolemma, the membrane of muscle fibers. ACh binds to ACh receptors, triggering the action potential to spread, and causing a release of calcium ions.
Botulinum Toxin Type A (BTX-A), is a Zn2+-dependent endoprotease neurotoxic protein obtained from the bacterium Clostridium botulinum. BTX-A produces muscle relaxation by binding to and entering the motor neuron where it cleaves SNAP-25, a SNARE protein. (Together with synaptobrevin and syntaxin, SNAP-25 is integral to the Ca2+-regulated exocytosis (release) of acetylcholine by the motor neuron.)
BTX-A was first approved by the US Food and Drug Administration for the treatment of strabismus, blepharospasm and hemifacial spasm in patients over 12 years old. In 2002, FDA approved BTX-A as a treatment for glabellar lines associated with corrugator and/or procerus muscle activity in patients 18 to 65 years of age. Inhibition of muscle contraction by BTX-A is reported to last typically for about four to six months.
It is known to those of ordinary skill in the art that muscle groups differ in their sensitivity to muscle relaxants. Muscles in the periorbital and glabellar areas are particularly sensitive to ACh and thus susceptible to effective treatment by agents that block Ach release. See, e.g., the review article published by L. Vimal and O. Oladapo, “Pharmacology of Non-Depolarising Muscle Relaxants” in Issue 5, Article 7 of Update in Anaesthesia, the electronic educational journal of World Anaesthesia and the World Federation of Societies of Anaesthesiologists. http://www.nda.ox.ac.uk/wfsa/html/u05/u05—012.htm accessed Jun. 20, 2007.
That certain edible solanaceous glycoalkaloid-containing plants (ESGPs)—in particular potatoes, eggplants, and tomatoes—increase the duration of action of anesthetics and muscle relaxants has been reported in the scientific literature. Researchers at the University of Chicago reported that potatoes, eggplants, and tomatoes inhibit the activity of enzymes that breakdown ACh and a structurally-related neurotransmitter butyrylcholine which acts on several Ach receptors. See, DS McGehee et al. “Cholinesterase Inhibition by Potato Glycoalkaloids Slows Mivacurium Metaboli” Anesthesiology, Vol. 93, No. 2, pp. 510-519 (August 2000).
Red and green peppers are edible solanaceous plants containing glycoalkaloids. P G Jones and G R Fenwick, “The glycoalkaloid content of some edible solanaceous fruits and potato products,” Journal of the Science of Food and Agriculture, Vol. 32, No. 4, pp. 419-421 (1981).
Ziziphus ziziphus (also known as Z. jujuba, Jujube, Red Date and Chinese Date) has long been cultivated in China. In the US, it is grown in the West (California and Utah), the Southeast (Alabama, Florida and Georgia) and the Gulf Coast (Texas and Louisiana). In traditional Chinese and Korean medicine, the Jujube fruit was ground into powder and ingested, reducing stress.
The mature Jujube fruit, which is dark red to purplish-black and wrinkled and thus similar in appearance to the date, is rich in alkaloids. See, R. Ziyaev et al., “Alkaloids of Ziziphus jujuba: the structure of juziphine and juzirine,” Chemistry of Natural Compounds, Vol. 13, No. 2, pp. 204-207 (1977); see also, M. Tripathi, “Cyclopeptide alkaloids from Zizyphus jujuba,” Fitoterapia, Vol. 72, No. 5, pp. 507-510 (2001). Z. jujube is listed on the ingredient labeling Age Defying Continual Eye Treat sold by Ahava.
U.S. Pat. No. 6,866,856 (assigned to Avon) teaches topical compositions comprising toosendanin and azadirachtin. (To the extent pertinent, the disclosures of all granted US patents and published US patent applications cited are incorporated in their entirety by reference.) Mechanistically, these two limonoid constituents are described in the '856 Patent as inhibiting acetylcholine release, thereby relaxing the muscles involved facial movement and expression. Topical application of formulations comprising one or both of these limonoid constituents are taught to ameliorate, reduce, and/or eliminate wrinkles and/or fine lines.
Laboratoires Sérobiologiques markets Myoxinol, a biotransformed oligopeptide derived from the seeds of Hibiscus esculentus L. (okra), as a “natural alternative” to Botox injections. According to marketing materials, the compound works by inhibiting facial muscle contraction, preventing the formation of horizontal and vertical frown lines, crow's feet and naso-labial lines.
US Patent Application Publication No. 2006/0275351 (assigned to Estée Lauder) describes a topical delivery system comprising a dermal patch that generates electrical current when in contact with the skin and a skin beneficial peptide (e.g., Myoxinol) in a conductive fluid.
US Patent Application Publication No. 2007/0065396 teaches topical compositions comprising macqui berry (as well as extracts and salts thereof) in combination with dermorelaxants, compounds which are defined as relaxing the muscles directly beneath the skin. Among the disclosed dermorelaxants are Myoxinol, the limonoid constituents taught in U.S. Pat. No. 6,866,856 and boswellia extract.
Argireline (INCI Name: acetyl hexapeptide-3) is marketed by Lipotec, SA and distributed in North America by Centerchem. A Jun. 18, 2004 article in the New York Times entitled “New Creams Smooth Wrinkles, But They're Not Botox” quoted the CEO of Centerchem who described Argireline as having a “de-stressing effect on the skin”. Among the many cosmetic products that contain Argireline are Revion's Age Defying Makeups with Botafirm (a complex comprising the acetyl hexapeptide and botanical extracts)
U.S. Pat. No. 6,169,074 teaches three peptide sequences that mimic the activity of neurotoxins produced by Clostridium botulinum and tetani. Structurally, the peptides are comprised of amino acid fragments from the substrate binding domains selected from three proteins which bind to form a receptor for docking of synaptic vesicles to the plasma membranes of neuronal cells (i.e., SNAP-25, VAMP-2 and syntaxin).
US Patent Application Publication No. 2007/0048245 teaches a topical composition comprising an extract of Acemella oleracea and a dermal stimulating peptide (particularly, short-chained palmitoylated, tri-, tetra- and penta-, and oligopeptides). The Acemella oleracea extract, described as rapid acting muscle relaxant, is claimed to limit contraction of facial muscles and thereby increase the efficiency of peptides in reducing wrinkles associated with photodamage and aging.
A number of skincare products claim to reduce wrinkles in a manner similar to BTX-A. Examples include Klein-Becker's Strivectin-SD®; Avon's Anew Clinical Deep Crease Concentrate with Bo-Hylurox. Some of these products have been described in the popular media as “faux-tox” creams. See, e.g., A. Cassabianca, “Freeze—The New Faux-Tox Creams” (describing Freeze 24/7, Dr. Brandt's Crease Release, Bliss's No-Motion Lotion and DDF's Wrinkle Relax serum as containing “topical muscle relaxants”) accessed on Jun. 20, 2007 www.filly.ca/health/beauty/skin_care/Freeze_Faux-Tox.asp.
Dr. Brandt's Crease Release and Dermadoctor's Immobile Lines products both contain gamma aminobutyric acid (GABA), a neurotransmitter that mediates muscle activation at the neuromuscular junction. According to the product description on the Dermadoctor website, Immobile Lines induces temporary topical muscle relaxation associated with facial expression, thereby visibly reducing expression lines near the eyes and on the forehead. See, http://www.dermadoctorskincare.com/immobilelines.html (accessed Jun. 20, 2007). Grant-X (formerly GranTox), an ingredient complex sold by Grant Industries, contains aminobutyric acid in combination with other botanical extracts (Panax ginseng, Portulaca oleracea and Centella asiatica). It is marketed as improving the appearance of facial fine lines and wrinkles.
Two product lines sold by L'Oréal and its Lancôme subsidiary, L'Oréal's Dermo-Expertise and Lancôme's Résolution D-Contraxol, claim a different muscle relaxant ingredient, magnesium gluconate. The February 2003 edition of Vogue, quotes Alan Meyers, Vice-President of R&D at L'Oréal USA: “Manganese [gluconate] has a relaxing effect on cells. When your face is flexing, it prevents the fibroblasts . . . from staying contracted.”
The prior art is replete with topical “anti-aging” compositions containing a plethora of active ingredients, many purporting to be naturally-derived from botanical sources (e.g., antioxidants, hydroxy acids, retinoids and short chain peptide derivatives) and claiming to help reduce the appearance of signs of extrinsic and intrinsic aging.
The uses of hydroxy acids for purposes of exfoliation, increasing skin cell turnover and helping to reduce the appearance of wrinkles are well known to those of skill in the art and are described, for example, in a series of related patents to Van Scott and Yu. See, U.S. Pat. Nos. 5,654,336; 5,547,988; and 5,385,938 (glycolic acid); U.S. Pat. Nos. 5,690,967; 5,684,044; 5,674,899; 5,547,988; and 5,422,370 (lactic acid); U.S. Pat. No. 5,889,054 (salicylic acid); U.S. Pat. Nos. 5,674,903; 5,547,988; and 5,470,880 (citric acid); U.S. Pat. Nos. 5,643,961 and 5,591,774 (malic acid).
A series of related patents assigned to Active Organics, LP—U.S. Pat. Nos. 5,976,556; 6,569,437; and 6,656,701—describe the uses of one or more acid protease enzymes in combination with an acidic buffering system that enhances epidermal exfoliation and/or epidermal cell renewal, thereby improving the texture or appearance of the skin.
In addition to topical products, and professional skin care treatments—including “light” cosmetic procedures performed by doctors, nurses, aestheticians and other trained technicians (e.g., micro-dermabrasion, chemical peels) and plastic surgery—consumers are increasingly seeking to treat the signs of aging through the use of ingested supplements, both in the form of capsules/tablets and beverages.
One example of an oral supplement taken by patients to decrease the appearance of aging is U.S. Pat. No. 5,804,594. The '594 patent teaches a method for the treatment and prevention of fine lines and wrinkles by oral administration of a pharmaceutical composition comprised of (i) a sugar compound that is converted to a glycosaminoglycan sufficient to thicken skin (e.g., N-acetylglucosamine), (ii) a primary antioxidant component in an amount sufficient to inhibit collagenase and elastase, (iii) at least one amino acid in an amount sufficient to assist in thickening skin (e.g., lysine or proline), (iv) a transition metal component in an amount effective to bind collagen and elastic fibers and thicken skin (e.g., zinc, manganese, copper), and (v) a catechin-based component in an amount sufficient to inhibit anti-collagen enzyme in the skin (e.g., a proanthocyanidin).
Commercially-available skin care nutritional supplements include: Murad Firm and Tone Dietary Supplement Pack (covered by the '594 patent); N. V. Perricone, M.D. Cosmeceuticals Skin & Total Body Dietary Supplements; RMX Essential from DDF.
The concept of skincare beverages is also known in the prior art. Borba has a line of nutraceutical water marketed as “Drinkable Skincare”. L'Oréal and Coca-Cola are reported to be collaborating on a tea-based beverage that provides skin benefits to be marketed under the brand name Lumaé. U.S. Pat. No. 6,375,992 (assigned to Procter & Gamble) further illustrates a beverage that provides skin benefits. The '992 Patent teaches a method of hydrating the skin and thereby decreasing the appearance of fine lines and wrinkles by administering a substantially decaffeinated oral composition comprising substantially decaffeinated green teas, one or more flavanols and at least two of aloe, glycerol, and red grape extract.
U.S. Pat. No. 5,869,540 (to W P Smith) teaches a method of reducing the appearance of deep lines by oral administration (in the form of a tea) of an herbal relaxant agent, an aqueous extract of valerian root. The '540 Patent further teaches a method for reducing the visible signs of aging induced by stress-related tension by topical administration of a composition comprising an aqueous extract of valerian (genus Valeriana), passion flower (genus Passiflora), mullein (genus Verbascum), skullcap (genus Scutellaria), lady's slipper (genus Cypripedium), magnolia (genus Magnolia), arrach (genus Atriplex) or comfrey (genus Symphytum). (Collectively, the above listed herbs are referred to, together with other herbs, as relaxant herbal agents (“RHAs”)). In addition, the '540 Patent teaches a combined method of treating stress-induced deep lines by a combination regimen of drinking valerian-infused tea and topically applying a composition comprising one of the above-listed RHAs.
The present invention is an improvement on the methods described in U.S. Pat. No. 5,869,540. RHAs not heretofore disclosed are claimed. Additionally, surprisingly and unexpectedly, it has been found that the administration of the RHAs disclosed in the '540 Patent in combination with ESGPs or edible glycoalkaloid-containing fungi (“EGFs”) and/or in combination with an exfoliating step, are more effective methods for reducing in the appearance of dynamic facial wrinkles.
For over two millennia, Valeriana officinalis has been used as a sedative and for the treatment of anxiety and insomnia. The predominant method of administering valerian has been and continues to be as a tea. Typically, from about 1.5 to about 3 grams of valerian root are steeped for five to ten minutes in 150 milliliters boiling water. Capsules have also been used, with a typical dose of from 300 to 1,800 milligrams by mouth. Medline Plus also reports use of valerian to treat stress, skin disorders, rheumatic pain, muscle pain, spasm and tension. See, www.nlm.nih.gov/medlineplus/druginfo/natural/patient-valerian.html accessed Jun. 20, 2007. See also, A. Herrera-Arellano, et al. “Polysomnographic evaluation of the hypnotic effect of Valeriana edulis standardized extract in patients suffering from insomnia” Planta Med. Vol. 67, pp. 695-699 (2001); P J Houghton, “The scientific basis for the reputed activity of Valerian” J. Pharm. Pharmacol. Vol. 51, pp. 505-512 (1999); P D Leathwood et al. “Aqueous extract of valerian root (Valeriana officinalis L.) improves sleep quality in man” Pharmacol. Biochem. Behav. Vol. 17, pp. 65-71 (1982).
U.S. Pat. No. 5,211,948 teaches a process for preparing powdered extracts of valerian root. The described process eliminates volatile odors produced by degradation products of valepotriates by adding an alcohol or acetone to the concentrated valerian extract. This step precipitates insoluble solids from the concentrated extract which are then separated from the extract. The extract is mixed with a carbohydrate and dried to obtain a powder.
U.S. Pat. No. 6,913,770 describes a process for isolating and purifying valerian extract by a hydroalcoholic extraction as well as the use of ingestible forms of valerian extract as a sedative, muscle relaxant and/or anxiolytic agent. U.S. Pat. Nos. 5,211,948 and 6,913,770 do not teach or suggest topical administration of valerian for reduction of dynamic facial lines.
The prior art teaches the use of mullein (Verbascum) as a muscle relaxant in treating asthma and other respiratory disorders involving irritation of the bronchi. See, http://www.asthmaforthelayman.com/herbs.htm. accessed on Jun. 20, 2007.
U.S. Pat. No. 6,287,567 teaches an herbal beverage for relieving symptoms of fatigue, congestion, fever and asthma comprising equal portions of comfrey root, comfrey leaf, rosehip, goldenseal, bee pollen, spearmint, chickweed, chamomile flower, catnip, mullein, pennyroyal, eucalyptus, and licorice root.
U.S. Pat. No. 6,814,987 teaches methods for preventing, treating, and managing sleeplessness, restlessness and weight gain due to stress or lack of sleep, by administration of magnolia extracts soluble in a lower alcohol, water or hydroalcohol mixture.
Quassia amara (also known as Amargo, Bitter Ash and Bitter Wood) is a deciduous tree found in rainforests from southern Mexico to Brazil. Its bark and wood contain triterpenes, indole alkaloids, quassinoids, canthinones and scopoletin, ingredients which have been reported in the ethnobotany literature as having anti-inflammatory, antiseptic, anti-neoplastic, anti-tumor, anti-viral and anti-parasitic properties. Extract of Q. amara is used in Aya Champu Espuma, a shampoo available from Nitropharma (Madrid, Spain) used to treat lice.
U.S. Pat. No. 5,676,949 teaches topical application of a simaba extract for depigmentation, promoting keratinocyte differentiation, improving cohesion of epidermal cells and more generally preserving or enhancing the protective function of skin and improving the quality of hair. The disclosed simaba species are in the same family (Simaroubaceae) as quassia species.
Elaeagnus angustifolia (also known as the Russian Silverberry, Oleaster, Trebizond Date and Russian olive) is native to western and central Asia and has been introduced to many areas of the US. Its fruit starts out yellow with silver scales and turns red as it ripens. Medicinal food uses of fruits in the genus Elaeagnus, including stopping and reversing the growth of cancers is reported in the scientific literature. See, Y S Lee et al. “Antioxidant Activity, Anti-Inflammatory Activity, and Whitening Effects of Extracts of Elaeagnus multiflora Thunb.” Vol. 10: No. 1, pp. 126-133 (2007). Lee et al. report that E. multiflora has anti-inflammatory and whitening (anti-tyrosinase) effects. The use of the fruit of E. angustifolia in traditional Iranian medicine as an analgesic and anti-inflammatory agent for joint pain has been reported. H. Hosseinzadeh and R. Rahimi, “Anti-Inflammatory Effects of Elaeagnus Angustifolia L. Fruits In Mice And Rats” Irn. J. Med. Sci. Vol: 24, No: 3&4, pp. 144-147.
Portulaca oleracea is an herbaceous weed with many common names including purslane, pig weed, little hogweed, pusley and vertolaga. Found in many regions of the world, it is rich in omega-3 fatty acids and protein, as well as many biologically active compounds including alkaloids, coumarins, flavonoids, saponin, tryptophan, anthraquinone glycosides, cardiac glycosides and free oxalic acids. In addition to being used as a sedative and analgesic, P. oleracea has been reported to be used for treating inflammatory conditions, hyperglycemic and hypertension. Reported dermatological uses include treatment of eczema and warts.
U.S. Pat. No. 7,060,303 (assigned to Avon) teaches a method for decreasing the number and/or depth of facial lines, wrinkles, creases or folds by topically applying to skin a composition comprising an effective amount of a purslane plant, which is taught to include P. oleracea. Portulaca is one of the ingredients in Avon's Anew Clinical Deep Crease Concentrate with Bo-Hylurox.
US Patent Application Publication No. 2004/0191208 (assigned to Clarins) teaches a cosmetic composition comprising a water-soluble extract of galangal (Alpinia officinarum), a water-soluble extract of buffalo grass (Hierochloe odorata), and a water-soluble extract of purslane (P. oleracea). The water-soluble extract of purslane is further taught to be an extract containing omega-3 fatty acids.
US Patent Application Publication No. 2005/0064049 (assigned to Kao) teaches forty active ingredients as stimulating or facilitating lipolysis of accumulated adipose tissue. Among these is purslane.
Myrciaria dubia (also known as the Camu camu and Rumberry) is a shrub found in swampy or flooded areas of the Amazon. Its fruits have a very high vitamin C content—thirty times as much vitamin C as an orange. It is also rich in iron, niacin, thiamin, riboflavin, phosphorus, potassium, beta-carotene, leucine, serine and valine. Nutritional supplements containing Camu camu claim this ingredient as helping to cure viral infections, influenza, the common cold, and autoimmune disorders, as well as aiding in weight loss.
U.S. Pat. No. 7,074,907 teaches a skin care preparation comprising an extract of a purity of at least 90% which is derived from one or more of camu camu fruit juice, camu camu fruit pericarp, camu camu seeds, and mixtures thereof. The disclosed composition is taught to have antioxidant and skin whitening properties.
US Patent Application Publication Nos. 2007/0065396 and 2006/0216251 (both assigned to Tracie Martyn International) teach camu berry as a plant extract rich in Vitamin C that may be incorporated in topical formulations. More particularly, the '396 Publication is directed to topical formulations comprising macqui berry as well as extracts and dermatologically acceptable salts thereof. The '251 Publication is directed to a composition comprising a lipoic acid, a carnitine and a carnosine, or dermatologically acceptable salts of each thereof. The compositions disclosed in both compositions are taught to include exfoliants, including alpha hydroxy acid.
The use of Platycladus orientalis (also known as Biota orientalis, Thuja orientalis and Oriental arborvitae) in traditional Chinese medicine was described in the 2700s BCE as calming the five vital yin organs. Prolonged use has been associated with improved complexion, more acute hearing and brightened eyes.
Amanita muscaria (also known fly agaric) is a white-spotted red mushroom. Ibotenic acid and muscimol, two constituents of A. muscaria, are structurally similar to the neurotransmitters glutamic acid and GABA. A. muscaria has also been described in the literature as an herbal muscle relaxant. See, e.g., Manderosian and Liberti eds., Natural Product Medicine, pp. 38-42 (Philadelphia, Pa.: G. F. Stickley, 1988). Mushrooms are also rich in glycoalkaloids. See, e.g., Pokorný J., “Natural toxic substances in food” Cas Lek Cesk. Vol. 136, No. 9, pp. 267-70 (May 7, 1997).
There remains a need for new and improved methods for reducing the appearance of dynamic facial wrinkles without invasive procedures such as injection or surgery. This need is met by the methods and compositions of the present invention.